Open Access

E3 ubiquitin ligase HRD1 modulates the circadian clock through regulation of BMAL1 stability

  • Authors:
    • Dongkai Guo
    • Yao Zhu
    • Hongfeng Wang
    • Guanghui Wang
    • Cheng Wang
    • Haigang Ren
  • View Affiliations

  • Published online on: July 10, 2020     https://doi.org/10.3892/etm.2020.8988
  • Pages: 2639-2648
  • Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Circadian rhythm serves an essential role in numerous physiological functions. Circadian oscillations are organized by circadian clock components at the molecular level. The precision of the circadian clock is controlled by transcriptional‑translational negative feedback loops, as well as post‑translational modifications of clock proteins, including ubiquitination; however, the influence of E3 ligases on clock protein ubiquitination requires further investigation. The results of co‑immunoprecipitation and immunofluorescent localization, indicated that the endoplasmic reticulum transmembrane E3 ubiquitin ligase HRD1, encoded by the synoviolin 1 gene, interacted with brain and muscle ARNT‑like 1 (BMAL1) and enhanced BMAL1 protein ubiquitination. In addition, the results of western blotting and reverse transcription‑​quantitative PCR suggested that HRD1 promoted K48‑associated polyubiquitination of BMAL1 and thus mediated its degradation via the ubiquitin‑proteasome system. Furthermore, gene knockdown and gene overexpression assays revealed that HRD1‑dependent degradation of BMAL1 protein regulated the expression of BMAL1 target genes and the amplitude of circadian oscillations in mammalian cells. The findings of the current study indicate that HRD1 may influence the regulation of circadian rhythm via modulation of BMAL1 stability.

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September-2020
Volume 20 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Guo D, Zhu Y, Wang H, Wang G, Wang C and Ren H: E3 ubiquitin ligase HRD1 modulates the circadian clock through regulation of BMAL1 stability. Exp Ther Med 20: 2639-2648, 2020
APA
Guo, D., Zhu, Y., Wang, H., Wang, G., Wang, C., & Ren, H. (2020). E3 ubiquitin ligase HRD1 modulates the circadian clock through regulation of BMAL1 stability. Experimental and Therapeutic Medicine, 20, 2639-2648. https://doi.org/10.3892/etm.2020.8988
MLA
Guo, D., Zhu, Y., Wang, H., Wang, G., Wang, C., Ren, H."E3 ubiquitin ligase HRD1 modulates the circadian clock through regulation of BMAL1 stability". Experimental and Therapeutic Medicine 20.3 (2020): 2639-2648.
Chicago
Guo, D., Zhu, Y., Wang, H., Wang, G., Wang, C., Ren, H."E3 ubiquitin ligase HRD1 modulates the circadian clock through regulation of BMAL1 stability". Experimental and Therapeutic Medicine 20, no. 3 (2020): 2639-2648. https://doi.org/10.3892/etm.2020.8988